Abundant and diverse bacterial species inhabit the GI tract, constituting the bulk of the GI microbiome. The GI microbiome plays key roles in health and disease processes throughout the body, yet it is unclear whether or how the microbiome mediates the pathogenesis of urologic chronic pelvic pain syndromes (UCPPS). Indeed, UCPPS cause significant morbidity in women and men, but etiologies, diagnostic markers, and therapies are lacking. Here, we present preliminary data demonstrating that UCPPS in women is associated with altered GI microbiota, and specific species are candidates for novel UCPPS biomarkers. Moreover, in clinically relevant murine UCPPS models, symptom-like behaviors can be modulated by manipulating the GI microbiome. We hypothesize that an altered GI microbiome results in circulating bacterial products that act on CNS targets and contribute to UCPPS. This project will use a combination of clinical, translational, and mechanistic studies to define the role of the GI microbiome in UCPPS, and in contrast to voiding dysfunction in the absence of pain. These findings will lead to the development of novel diagnostics and effective probiotic therapies for chronic pelvic pain.